Decalone reduction

The Birch reductions of C C double bonds with alkali metals in liquid ammonia or amines obey other rules than do the catalytic hydrogenations (D. Caine, 1976). In these reactions regio- and stereoselectivities are mainly determined by the stabilities of the intermediate carbanions. If one reduces, for example, the a, -unsaturated decalone below with lithium, a dianion is formed, whereof three different conformations (A), (B), and (C) are conceivable. Conformation (A) is the most stable, because repulsion disfavors the cis-decalin system (B) and in (C) the conjugation of the dianion is interrupted. Thus, protonation yields the trans-decalone system (G. Stork, 1964B). 

In this experiment, advantage is made of the fact that lithium-ammonia reduction usually proceeds to give trans-fused Decalins 4). Thus, hydrogenation of A -octal one-2 over palladium catalyst gives essentially cw-2-decalone as the product, whereas the lithium-ammonia reduction of the octalone gives the trans ring fusion. 

Mesylation of alcohol 14 and hydrolysis of the acetal with oxalic acid leads to the key decalone 16 which cyclises in the presence of NaH in dioxane to afford twistanone 17 in quantitative yields. The elimination of the carbonyl group was carried out by an alternative method to the Wolff-Kishner reduction, which involves the thioacetalisation of the twistanone (18) with ethane-1,2-dithiol and removal of the resulting thioacetal by Raney nickel in boiling ethanol (62% yield). 

Cotton effects of c/.t-decalones bearing no structural features which stabilize a particular conformer are likely to be due to contributions from both steroid-like and nonsteroid conformers. The absolute ring configurations of hydroxydecalones prepared by stereospecific HLAD catalyzed reductions of decalindiones follow from the measurement of the n-7t Cotton effect35 ... 

Alkylations of tran.v-2-decalone enolates 30 have been performed with high degrees of diastereose-lectivity. 1,3-Interactions are clearly very important steric-control elements in the angularly substituted compounds. The examples shown also demonstrate that reductive alkylations of a,/ -unsaturated ketones are a useful diastereoseleclive step in the syntheses of polycyclic compounds19 11 7S-80. 

The reduction of 212 (R=H) gives a mixture of trans and cij> decalones 219 and 220 (R=H) in a 99 1 ratio (63). An analysis of non-bonded interactions in the corresponding enolates 216 and 217 (R=H) indicates that the former should be favored only by about 1.0 kcal/mol, which should correspond to an approximately 80/20 trans/cis ratio. This result indicates that there is a significantly greater preference for the trans species 21 6 than would be predicted by analysis of non-bonded interactions. 

The above stereoelectronic arguments were proposed by Stork and Darling (61) to explain why the more stable isomer is not necessarily always obtained (62). For example, reduction of the octal one 221 with lithium-ammonia-ethanol followed by oxidation afforded the trans-2-decalone 222 even though the isomeric cis-2-decalone 223 is about 2 kcal/mol more stable than 222. Conformation 226 of the enolate dianion is the most favored sterically but it is electronically disfavored. Conformations 224 and 225 are both electronically favored but 225 is less favored sterically than 224. Therefore,... 

The large steric requirement of L-Selectride generally favors reduction of cyclohexanones to form axial alcohols. However, in this cw-decalone example, the formation of the axial alcohol is hindered by the adjacent ring. 

This stereochemistry is similar to that in the reduction of a,/3-unsaturated ketones. Stork found that octalones like 7.88 were reduced exclusively to the frans-decalone 7.90, even in cases when the trans- was less stable than the corresponding c/.v-decalin. In this reaction, an electron is fed into the LUMO... 

Wu, Y.-D. Tucker, J. A. Houk, K. N. Stereoselectivities of nucleophilic additions to cyclohexanones substituted by polar groups. Experimental investigation of reductions of trans-decalones and theoretical studies of cyclohexanone reductions. The influence of remote electrostatic effects, J. Am. Chem. Soc. 1991,113, 5018-5027. 

Correct reagent selection allowed reduction of steroidal enone (74) to either diastereoisomeric allylic alcohol, uncontaminated by its isomer. Sodium borohydride/cerium chloride in methanol-THF gave the equatorial alcohol (73), while L-selectride produced the axial isomer (75) via equatorial attack (Scheme 12). Unexpected axial attack on diketone (76) to give equatorial alcohol (77 equation 19) led to the proposition that for hydride additions to decalones two 1,3-diaxial interactions override one peri interaction which in turn takes precedence over a single 1,3-diaxial interaction. ... 

The other group of moderately hindered cyclohexanones which has been examined in detailed is a group of substituted 1-decalones, which gave results similar to those of the 12-keto steroids on Li-NHs reduction. These decalones were all derived from protected diketone (51) and included two different 2-monosubstituted derivatives (52) and (53). These decalones were reduced both in the presence of a proton donor (NH4CI) and under anhydrous conditions in yields of 69-99%. The axial alcohol was the major product in the presence of a proton donor, while the equatorial alcohol was predominant in its ab-... 

The reductions of 1- and 12-keto steroids and their 1-decalone derivatives graphically illustrate the fact that dissolving metal reductions of ketones do not necessarily afford the more stable of a pair of epimeric alcohols. As a corollary, while the reduction of cyclic ketones is a synthetically useful procedure for the stereoselective preparation of secondary alcohols, it cannot be assumed that the thermodynamically stable alcohol will be the product which is obtained stereoselectively. 

Enantiomeric and diastereotopic face specific reductions are also readily effected on racemic bicyclic ketones. An illustration of the broad structural range that is amenable to enzyme-catalyzed transformation in this way is given in Scheme 38. While 2-decalones, such as ( )-(81)- 83), and the related heterocyclic analogs ( )-(85) are good substrates for HLADH, the 1-decalone ( )-(84) is not. However, by changing enzymes to MJADH, ( )-(84) becomes a good substrate.Similarly, TBADH is a highly satisfactory catalyst for stereospecific reduction of ( )-(86), but will not accept its dimethyl... 

The ease and the stereochemical course of hydrogenation of a,p-unsaturated ketones are particularly influenced by the nature of the solvent and the acidity or basicity of the reaction mixture. Some efforts have been made to rationalize the effect of the various parameters on the relative proportions of 1,2- to 1,4-addition, as well as on the stereochemistry of reduction. For example, the product distribution in -octalone hydrogenation in neutral media is related to the polarity of the solvent if the solvents are divided into aprotic and protic groups. The relative amount of cis- -decalone decreases steadily with decreasing dielectric constant in aprotic solvents, and increases with dielectric constant in protic solvents, as exemplified in Scheme 21 (dielectric constants of the solvents are indicated in parentheses). Similar results were observed in the hydrogenation of cholestenone and of testosterone. In polar aprotic solvents 1,4-addition predominates, whereas in a nonpolar aprotic solvent hydrogenation occurs mainly in the 1,2-addition mode. 

The diamond lattice model (Figure 7) was developed using six-membered ring ketone substrates. The determination of forbidden and undesirable positions was achieved by analysis of the relative rates of reduction of a series of cyclohexanones and decalones of known absolute configuration. The geometry indicated at the C-0 centre was considered to resemble the structure of the alcohol rather than that of the ketone in the transition state. It was assumed that all substrate molecules bound with oxygen in the... 

It is noteworthy that reduction of the a,(3-unsaturated decalone shown below with lithium in liquid ammonia furnishes the fran -decalone as the major product in spite of the 1,3-diaxial interaction between the CH3-OCH3 substituents. ... 

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